Targeting the mPGES-PGE2-EP4 pathway with MF63, MK886, and Grapiprant as a potential therapeutic strategy for Escherichia coli-induced endometritis in dairy cows
文献类型： 外文期刊
作者： Yang, Xiaolin 1 ; Guo, Lili 1 ; Gong, Pengfei 1 ; Wu, Jingze 1 ; Qian, Yinghong 4 ; Zhang, Shuangyi 1 ; Guo, Wenrui 1 ; Cao, Jinshan 1 ; Feng, Shuang 1 ; Mao, Wei 1 ;
作者机构： 1.Inner Mongolia Agr Univ, Key Lab Clin Diag & Treatment Tech Anim Dis, Minist Agr, 29 Erdosdong Rd, Hohhot 010011, Peoples R China
2.Inner Mongolia Agr Univ, Coll Vet Med, Lab Vet Clin Pharmacol, 29 Erdosdong Rd, Hohhot 010011, Peoples R China
3.Inner Mongolia Bayannaoer City Municipal Ctr Dis C, Hohhot 015002, Peoples R China
4.Inner Mongolia Acad Agr & Anim Husb Sci, Hohhot 010031, Peoples R China
关键词： Escherichia coli; Endometritis; Prostaglandin E 2; MF63; MK886; Grapiprant
期刊名称：THERIOGENOLOGY （ 影响因子：2.5； 五年影响因子：2.7 ）
ISSN： 0093-691X
年卷期： 2026 年 249 卷
页码：
收录情况： SCI
摘要： Escherichia coli (E. coli) is the primary causative agent of endometritis in dairy cows. Antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs) are the main treatments; however, prolonged antibiotic use promotes bacterial resistance, while NSAIDs can delay ovulation and impair reproduction. Safer and more effective alternative therapies are needed to control infection while minimizing adverse effects. In the bovine uterine microenvironment, prostaglandin E2 (PGE2) plays a key role by activating the EP4 receptor. However, the therapeutic potential of microsomal prostaglandin E synthase-1 (mPGES-1) inhibitor (MF63), mPGES-1 regulator (MK886) and the EP4 receptor antagonist (Grapiprant) in bacterial endometritis remains unclear. This study investigates the therapeutic potential of MF63, MK886 and Grapiprant in mitigating E. coli-induced endometritis in dairy cow. Molecular docking showed that MF63 and MK886 efficiently bind to mPGES-1, while Grapiprant stably binds to the EP4 receptor. Additionally, these inhibitors significantly suppressed PGE2 secretion in E. coli-infected bovine endometrial tissues. Hematoxylin and eosin staining and immunofluorescence analysis demonstrated that MF63, MK886, and Grapiprant significantly reduced E. coli-induced tissue damage and the expression of damageassociated molecular patterns, such as HMGB-1 and HABP-2. Furthermore, these treatments decreased proinflammatory cytokines (TNF-alpha, IL-6, IL-1 beta) and the chemokine IL-8 while increasing IL-10 expression. In conclusion, targeting the mPGES-PGE2-EP4 pathway may offer a safer, more effective alternative for managing E. coli-induced endometritis in dairy cows.
- 相关文献
作者其他论文 更多>>
-
Egg yolk-derived low-density lipoprotein: A potential drug delivery system to eradicate intracellular bacteria
作者：Zhao, Yi;Liu, Bo;Zhang, Shuang-yi;Wang, Yong-fei;Hasi, Su-rong;Gong, Zhi-guo;Zhao, Jia-min;Yang, Xiao-lin;Bai, Yu-ting;Cao, Jin-shan;Mao, Wei;Zhao, Yi;Liu, Bo;Zhang, Shuang-yi;Gong, Zhi-guo;Zhao, Jia-min;Yang, Xiao-lin;Cao, Jin-shan;Mao, Wei;Wang, Yong-fei;Qian, Ying-hong
关键词：Hen egg low-density lipoprotein; Ceftiofur; Intracellular drug delivery system; Staphylococcus aureus
-
Investigating the role of the mPGES-PGE2-EP4 pathway in Escherichia coli-induced mastitis in dairy cows: insights for non-antibiotic therapeutic strategies
作者：Yang, Xiaolin;Li, Xueqiang;Guo, Lili;Gong, Pengfei;Zhang, Shuangyi;Liu, Bo;Guo, Wenrui;Bao, Haixia;Mao, Wei;Yang, Xiaolin;Li, Xueqiang;Guo, Lili;Gong, Pengfei;Zhang, Shuangyi;Liu, Bo;Guo, Wenrui;Bao, Haixia;Mao, Wei;Gong, Pengfei;Qian, Yinghong
关键词：
Escherichia coli ; mastitis; alternative treatments to antibiotics; mPGES-1 inhibitors; EP4 receptor inhibitor -
Regulatory Effect of PGE2-EP2/EP4 Receptor Pathway on Staphylococcus aureus-Induced Inflammatory Factors in Dairy Cow Neutrophils
作者：Zhao, Yi;Wang, Chao;Liu, Bo;Zhang, Shuangyi;Wang, Yongfei;Gong, Zhiguo;Zhao, Jiamin;Yang, Xiaolin;Bai, Yuting;Mao, Wei;Zhao, Yi;Wang, Chao;Liu, Bo;Zhang, Shuangyi;Gong, Zhiguo;Zhao, Jiamin;Yang, Xiaolin;Wang, Yongfei;Qian, Yinghong
关键词：neutrophils of cows; Staphylococcus aureus Rosenbach; prostaglandin E-2; EP2/EP4 receptor pathway; anti-inflammatory therapy
-
The effect of taurochenodeoxycholic acid on the glucocorticoid receptor-mediated PLC-IP3-calcium pathway in synoviocytes derived from a rat adjuvant arthritis model
作者：Guanqia, Sangjide;Li, Peifeng;Cao, Jinshan;Mao, Wei;Wu, Jindi;Guanqia, Sangjide;Li, Peifeng;Cao, Jinshan;Bai, Fan;Qian, Yinghong;Mao, Wei
关键词：taurochenodeoxycholic acid; rat adjuvant arthritis model; glucocorticoid receptor; phospholipase C-inositol trisphosphate-Ca2+ signalling pathway
-
Prostaglandin E2 accumulation is closely associated with S. aureus-infected bovine endometritis
作者：Liu, Kun;Shen, Yuan;Zhang, Nan;Liu, Kun;Shen, Yuan;Wu, Jindi;Mao, Wei;Cao, Jinshan;Pei, Le;Qian, Yinghong
关键词：Endometritis; S. aureus infection; Prostaglandin E2; Immunology
-
Massively Parallel CRISPR-Cas9 Knockout Screening in Sheep Granulosa Cells for FSH Response Genes
作者：Liu, Zaixia;Dai, Lingli;Bao, Yanchun;Gu, Mingjuan;Shi, Caixia;Zhou, Le;Ma, Fengying;Na, Risu;Zhang, Wenguang;Liu, Zaixia;Dai, Lingli;Bao, Yanchun;Gu, Mingjuan;Guo, Lili;Zhou, Le;Ma, Fengying;Na, Risu;Zhang, Wenguang;Dai, Lingli;Sun, Tianhao;Liu, Yongbin;Fu, Shaoyin;He, Xiaolong;Wang, Yu;Guo, Lili;Zhang, Wenguang
关键词：granulosa cells; FSH; massively parallel CRISPR-Cas9 library; dose-dependent genes
-
Preparation of ceftiofur-encapsulated hen-egg low-density lipoproteins and their antibacterial effects on intracellular Staphylococcus aureus
作者：Zhao, Yi;Mao, Wei;Liu, Bo;Wang, Yong-fei;Zhang, Shuang-yi;Guo, Li-li;Gong, Zhi-guo;Zhao, Jia-min;Yang, Xiao-lin;Qu, Gang-gang;Hasi, Su-rong;Bai, Yu-ting;Cao, Jin-shan;Zhao, Yi;Mao, Wei;Liu, Bo;Wang, Yong-fei;Zhang, Shuang-yi;Guo, Li-li;Gong, Zhi-guo;Zhao, Jia-min;Yang, Xiao-lin;Qu, Gang-gang;Bai, Yu-ting;Cao, Jin-shan;Wang, Yong-fei;Qian, Ying-hong
关键词：Hen-egg low-density lipoprotein; Ceftiofur; Intracellular drug delivery system; Staphylococcus aureus
